Membranes Flashcards
1
Q
What is a cell membrane and what is it good for?
A
- Compartmentalization (essential for life)
- Maintain disequilibrium (ions, biomolecules)
- Mechanoprotection and mechanosensation
- Chemosensation
- Excitability
Most importantly - the cells interface with the external world
The cell membrane is the cell’s interface with the external world.
2
Q
What do bacteria and plant cells have that protects their inner cell membrane?
A
A hard rigid cell wall
This provides structural support and protection.
3
Q
What is the simplest cell-like structure?
A
A lipid bilayer vesicle
It serves as a model for studying cell membrane properties.
4
Q
What stabilizes the lipid bilayer?
A
- Van der Waals forces
- Hydrophobic effect
- Hydrogen bonds with water molecules
These interactions help maintain the integrity of the membrane.
5
Q
How thick is a typical lipid bilayer?
A
3-4 nm
This is significantly thinner than a soap bubble, which is 400-700 nm thick.
6
Q
Is the lipid bilayer passive or active?
A
Passive substrate or neutral solvent for membrane proteins
However, it is not impermeable; significant water movement occurs.
7
Q
True or False: A single Na+ ion crosses the lipid bilayer every 70 hours.
A
True
This indicates low permeability for ions.
8
Q
What technique is best to study the mechanical properties of a lipid bilayer?
A
Pipette aspiration technique
This allows observation of vesicle deformation.
9
Q
What do intrinsic mechanical properties of a vesicle refer to?
A
Material elastic properties
These properties remain constant regardless of the vesicle’s state of inflation.
10
Q
What is the effect of osmotically inflating a vesicle?
A
Limited deformability; can only expand in area by 2-5% before rupture
Expansion leads to proportional thinning of the bilayer.
11
Q
What is a major function of the cytoskeleton in animal cells?
A
To provide resistance to shear
This allows cells to maintain shape and stability.
12
Q
How do biological lipid membranes differ from artificial lipid vesicles?
A
Composed of many different types of lipid molecules
Over 100 different phospholipid species are present in mammalian cells.
13
Q
What role do lipid rafts play in biological membranes?
A
Act as signaling platforms utilized by viruses like HIV
They facilitate specific interactions between membrane proteins.
14
Q
What is hydrophobic mismatch?
A
The energy difference between the bilayer and hydrophobic region of a protein
It affects the stability and function of membrane proteins.
15
Q
What is Gramicidin and its significance?
A
An antibiotic that forms ion-conducting channels
It illustrates the interaction between bilayer properties and protein function.
16
Q
What does PLC stand for and its role?
A
Phospholipase C; hydrolyzes PI(4,5)P2 to generate second messengers
This process is crucial for various signaling pathways.
17
Q
What are the two second messengers generated by PLC?
A
- Diacylglycerol (DAG)
- Inositol 1,4,5-trisphosphate (IP3)
DAG activates protein kinase C, while IP3 stimulates Ca2+ release.
18
Q
What is the role of specific enzymes like flippase, floppase, and scramblase?
A
They redistribute lipids within the bilayer
This redistribution can signal critical cellular processes.
19
Q
What is the importance of lipid head group charge?
A
Affects membrane protein distribution and packing
This can influence membrane fluidity and functionality.
20
Q
rule number 1
A
when things are too complex, simplify
21
Q
the head of a lipid is
A
polar/hydrophillic
22
Q
the tail of a lipid is
A
nonpolar/hydrophobic
23
Q
the fatty acid chain is usually
A
C-18
24
Q
the bilayer forms two monolayers stabilized by
A
vanderwaals forces and the hydrophobic effect between the hidden acyl chains
25
water molecules surround the lipid head group and
form hydrogen bonds that further stabilize the bilayer
26
why does the lipid bilayer form a sphere
more energentically favorable
no edges exposed to water
27
how thick is a soap bubble
400-700nm
28
the lipid bilayer is a passive substrate or a neutral solvent for
the functionally important membrane proteins that are embedded in it
29
rule number 2
dont let any old dogma lick you
30
Is the bilayer really passive (i.e., is it just an immobile, impermeable barrier)?
No! An estimated 4000 water molecules pass a single phospholipid molecule per second. They do so by hopping between the acyl chain packing defects (e.g., trans-gauche kinks).
31
is the lipid bilayer ion permeable
no
32
How can we measure the mechanical properties of a bilayer when its thinner and more fragile than a soap bubble?
Best to study a lipid vesicle (i.e., the simplest cell like structure)
Use a pipette aspiration technique.
33
How a lipid vesicle responds to deformation depends upon
Extrinsic properties (i.e., size and geometry)
Intrinsic properties (i.e., material elastic properties
34
Intrinsic mechanical properties
characterized by elasticity constants,
35
Extrinsic mechanical properties
Whether it is inflated or deflated the intrinsic (material properties) are the same
36
What is the deformability comparison between an osmotically deflated vesicle and an inflated vesicle?
An osmotically deflated vesicle is more deformable than an inflated vesicle
37
What happens to a deflated vesicle over time?
It is unstable and will tend to bud or vesiculate
38
What is the maximum area expansion percentage for an osmotically inflated vesicle before it ruptures?
2-5%
39
What must accompany any expansion in area of a bilayer?
A proportional thinning of the bilayer
40
How is the bilayer described in terms of compressibility?
It can be considered an incompressible solid
41
What analogy is used to describe the behavior of an expanding bilayer?
An expanding balloon that thins as it expands
42
What type of resistance do vesicles show?
Little resistance to bending or surface shear
43
True or False: Vesicles have significant resistance to bending.
False
44
Why is the next level of complexity in a cell membrane, the cytoskeleton, necessary
a major function of the cytoskeleton in animal cells
is to provide resistance to shear
45
What do elaborate, dynamic cytoskeletal networks organize?
The cell membrane shape and regulate numerous processes
## Footnote
Cytoskeletal networks are essential for various cellular functions.
46
What remarkable specializations can cells achieve due to the cytoskeletal networks?
Structural and functional specializations
An example is the bushy dendritic tree of the cerebellar Purkinje cell.
## Footnote
An example is the bushy dendritic tree of the cerebellar Purkinje cell.
47
How many synapses can the dendritic tree of a cerebellar Purkinje cell receive?
100,000 synapses
## Footnote
This illustrates the complexity and connectivity of neuronal structures.
48
What shape could a cell only assume without a cytoskeleton?
A simple spherical shape
## Footnote
The cytoskeleton is crucial for maintaining cell shape and function.
49
What are biological lipid membranes composed of?
Many different types of lipid molecules, including over 100 different phospholipid molecular species in mammalian cells and tissues.
## Footnote
This diversity contributes to the functionality of lipid membranes.
50
What is the role of sphingolipids and cholesterol in biological membranes?
They preferentially pack into floating platforms or 'rafts' of lipids that can be isolated as detergent-insoluble membrane complexes.
## Footnote
These rafts play a key role in cellular signaling and membrane organization.
51
How are the monolayers of biological bilayers characterized?
They are highly asymmetrical in terms of their lipid composition.
## Footnote
This asymmetry is crucial for various membrane functions.
52
What does the term 'flip-flop' refer to in the context of lipid membranes?
The movement of a lipid molecule from one layer of the bilayer to the other.
## Footnote
This process would require the hydrophilic head group to move through a hydrophobic environment.
53
target for covid treatment
ACE2 receptor
54
after the lipid components, what is the next major component in the membrane heirarchy
proteins
55
what is hydrophobic mismatch
Hydrophobic mismatch is the difference in thickness between the hydrophobic regions of a transmembrane protein and the surrounding lipid bilayer. It can occur when the protein's hydrophobic segments are too long or too short compared to the bilayer's hydrophobic thickness
56
positive and negative mismatch increases the
energy of the bilayer-protein complex by promoting deformation of the acyl chains
57
we can understand hydrophobic mismatch using
a stretch activated channel
gramacidin
58
gramacidin channel formation depends upon
dimerization of monomers in each monolayer
59
in a thick bilayer (20C) gramicidin is
stretch activated
60
in a thin bilayer (18C) gramicidin is
stretch inactivated
61
the applied membrane stretch of the gramacidin in the thick membrane
thins the thick bilayer and is more compatible with ion-conducting dimers
62
the applied membrane stretch of the gramacidin in the thin bilayer
further thins the bilayer making it less compatible with ion conducting dimers
63
the bilayer can adjust its thickness in order to
energetically
promote specific functional membrane protein conformations by using Its many different lipids (i.e., each protein surrounded by specific lipids)
64
how important are mechanosensitive or stretch activated channels?
very
Touch sensation
Pain
Hearing
Cell volume regulation (i.e., stretch activated K+ channels)
and even implicated in concussion and traumatic brain injury
65
why is ardem smiling
he won the Nobel Prize for the discovery of thermal and mechanical transducers
66
what is piezo
a mechanically gated channel
Piezo ion channels are nonselective cation channels that are activated by mechanical forces. They are the largest ion channels known to exist in the plasma membrane
67
what happens when there is a mutation in Piezo
when the eyes are closed, spacial awareness and walking is impossible
68
many plasma membrane ion channels and transporters require
PIP2 to function and can be turned off by signaling pathways that deplete PIP2.
69
what cleaves PIP2
phospholipase C (PLC)
70
Specific phospholipids of biological bilayers contribute directly to
signaling via the action of phospholipases that generate 2nd messengers by degrading/cleaving the phospholipids.
71
Phospholipase C (PLC) hydrolyzes PI(4,5)P2 to generate:
Diacylglycerol (DAG) that activates protein kinase C
Inositol 1,4,5,-trisphosphate (IP3) that stimulates Ca2+ release from ER stores.
But PIP2 itself is required by a wide variety of channels so that PLC by removing PIP2 can inactivate channels (i.e., by the muscarinic M1 receptor) or is required for the channel to be opened (i.e., by the M2 receptor)
72
Evidence against the passive bilayer and for a dynamic structure
Many different lipids asymmetrically distributed within the bilayer by highly specific enzymes (flippase, floppase and scramblase) and their redistribution can be a critical signal
(i.e., cell death)
Bilayer thickness affects membrane protein function via hydrophobic mismatch. Charge on lipid head groups can affect membrane protein distribution and packing.
Lipid rafts form signaling platforms “rafts” that draw specific membrane enzymes and receptors together into a signaling complex.
Specific lipases degrade membrane phospholipids into
2nd messenger molecules (e.g., PIP2, IP3 and diacylglycerol)
73
on the permeability scale, where does glucose fall?
in the middle
74
two mechanisms of passive transport
membrane ion channel
carrier protein - moves down concentration gradient
75
membrane ion channels transport
fast
76
carrier proteins transport
slow due to the conformational change
77
if the solute moves down its concentration gradient then
no energy is required
78
how does glucose move against its concentration gradient?
cotransporter
uses Na gradient created from the NaK pump
79
the NaK pump uses what to create a Na gradient
ATP
80
where is the high Na concentration gradient made
high outside the cell
81
NaGlucose carrier
uses the Na gradient and glucose hitches a ride from low outside to high inside
82
Primary active transport
"uphill" solute transport directly coupled to an exergonic chemical reaction, e.g., ATP hydrolysis.
83
an example of primary active transport
NaK pump
84
secondary active transport
"uphill" solute transport is coupled to "downhill" transport of a
different solute whose gradient was established (is maintained) by primary active transport
85
example of secondary active transport
NaGlucose
86
uniport
systems that transport only one solute
87
cotransporter
transport of 2 solutes at the same time
88
symport
cotransported solutes go in the same direction
89
antiport
cotransported solutes move in opposite directions
90
how does glucose move from the gut to the blood?
1. Glucose import from intestine made possible by Na+-glucose symporter that enables epithelial cells to concentrate glucose from intestine to 30,000 x the intestinal concentration
2. The high concentration of glucose within cell passes "down" its concentration gradient through
basal surface of cell into blood via GluT2 transporter (facilitated diffusion, uniport system).
91
what has been used to treat cholera
Gatorade
92
the sodium content of gatorade is
450mg/L
93
How is insulin secreted
1. jelly donut is eaten
2: Glucose enters the cell
via the Glut 2 uniporter down its
concentration gradient
3: Glycolysis raises [ATP]in
4: increased ATP blocks K+ channels causing depolarization
5: Depolarization opens voltage Ca2+ channels causing elevation of [Ca2+]i
6: increased Ca2+ causes exocytosis of vesicles containing insulin
94
sulfonylurea drugs block
K=ATPm channels used to treat type II diabetes
95
the technique that enabled the discovery of the K+ATP channel
cell-free patch clamp recording
96
in skeletal muscle, in the absence of insulin
glucose cannot enter the cell
97
in skeletal muscle, insulin signals the cell to
insert GLUT 4 transporters into the membrane allowing glucose to enter the cell
98
in the absence of insulin, how can GLUT4 be inserted into the membrane
stretching muscles
99
general water considerations
Water goes down its chemical gradient
Chemical potential of water is composed of a concentration component and a hydrostatic component
The chemical potential of water is inversely related to the chemical potential of dissolved stuff
And depends mostly on the number of particles, not their character
100
osmolarity/osmolality
Osmolarity is the concentration of particles in a solution per liter, while osmolality is the concentration of particles in a solution per kilogram. Osmolality is the preferred term for biological systems because it is temperature independent
101
osmolarity is compared to
a reference solution - usually blood plasma
102
osmolarity is considered ohysical chemistry and is measured with
an osmometer
no cells involved
103
osmolarity/osmolality is what kind of property
colligative
104
isoosmotic
same osmolarity as the reference solution
105
hypoosmotic
less than reference
106
hyperosmotic
more than reference
107
tonicity refers to
what a given solution does to a particular cell’s volume (usually at steady state)
108
isotonic solution
leaves cell volume intact
109
hypotonic solution
expands cell volume
110
hypertonic solution
decreases volume
111
volume regulation in response to cell shrikage and swelling
regulates via orchestration of channels and pumps all dependent on the NaK pump
112
how do we know that there is a water channel
water permeability is million times greater than it could be with the bilayer alone
113
who discovered the aquaporin
Peter Agre
114
where does serendipity come from
Serendipity comes from a fairy tale “The three Princes of Serendip” who were always making discoveries by accident and sagacity.
Sagacity (often forgotten) means a penetrating intelligence, keen perception and sound judgment.
115
what was the aquaporin named before
Chip 28
channel forming integral protein
116
when aquaporin mRNA is injected into a frog oocyte
water influx dramatically increases causing lysis
117
where is aqp2
kidney
118
where is aqp4
brain and muscle
119
water crosses cell membranes by two routes
by diffusion through the lipid bilayer and through water channels called aquaporins.
120
why were water channels suspected to exist
because the osmotic permeability of some types of epithelial cells (e.g., kidney) was much too large to be accounted for by simple diffusion through the plasma membrane.
121
the first aquaporin
Functional characterization of the first aquaporin was reported in 1992 by Peter Agre (Nobel prize winner) but in reality Benga et al. were first in1986
122
a single aquaporin 1 channel facilitates water transport at a rate of
3 billion water molecules per second
123
water transport in aquaporins should be
bidirectional in accordance with the prevailing osmotic gradient
124
The classical aquaporins transport solute-free water across cell membranes; they appear to be exclusive water channels and do not allow permeation of
Na+ K+, Cl- ions, hydronium or other small molecules.
125
what in the aquaporin channel allow for water to pass but not anything else
two asparagine-proline-alanine (NPA)
126
water reabsorption in the kidney
Blood is filtered at the glomerulus, and the filtrate is modified as it travels through the nephron to make the final urine.
Most of the glomerular filtrate is resorbed through aquaporin-1 (AQP1) in the proximal tubule and descending thin-limb epithelial cells, although AQP7 and AQP8 are also present in the proximal-tubule epithelium.
Endothelial cells of the descending vasa recta contain AQP1, which facilitates the removal of water to maintain hypertonicity in the interstitial space.
In the collecting duct, the hormone vasopressin (ADH: anti-diuretic hormone) increases membrane water permeability by stimulating the redistribution of AQP2 from cytoplasmic vesicles to the apical membrane of principal cells.
127
aqp3 and aqp4 are present on what in the kidney
the basolateral membrane of principal cells
128
aqp6 is present in
intracellular vesicles of the acid-secreting intercalated cells
129
in the collecting ducts in the kidney the water can go one of two ways
be voided in the urine
be reabsorbed across the epithelium and back into the blood
130
reabsorption is essentially nil unless the epithelial cells see
antidiuretic hormone, which strongly stimulates reabsorption of water.
131
collecting duct cells express what two aquaporins
2 and 3
132
aquaporin 2 in collecting ducts
in the absence of antidiuretic hormone, resides in a pool of membrane vesicles within the cytoplasm. Binding of antidiuretic hormone to its receptor in the cell not only stimulates transcription of the aquaporin-2 gene, but causes the intracellular pool of aquaporin-2 to be inserted into the apical membrane. The cell is now able to efficiently take up water from the lumen of the duct.
133
aquaporin 3 in the collecting ducts
Aquaporin-3 is constitutively expressed in the basolateral membrane of the cell. When water floods into the cell through aquaporin-2 channels, it can rapidly exit the cell through the aquaporin-3 channels and flow into blood.
134
what does alcohol do in terms of water retention
Ethanol inhibits ADH release from pituitary blocking insertion of aquaporin2 into the membrane of the collecting duct so that water is not reabsorbed thereby increasing the volume of urine
135
peripheral lymphatics
a drainage system for the body
136
glymphatic system
The glymphatic pathway is a specialized system in the brain responsible for clearing metabolic waste and maintaining fluid balance. It is analogous to the lymphatic system in the rest of the body but operates within the central nervous system.
137
components of the glyphatic system
The components of the glymphatic system include the cerebrospinal fluid, interstitial fluid, AQP4 channels, perivascular spaces (Virchow-Robin spaces), and the venous draining system.
138
steps of the glymphatic system
First the cerebral spinal fluid enters the brain through the periarterial space, then using the AQP4 channels, the cerebral spinal fluid mixes with the interstitial fluid, and waste products such as amyloid-beta are picked up. Then the fluid is transported out of the brain along the perivenous spaces to the venous draining system.
139
Because the Glymphatics only opens during sleep a good nights sleep is a possible way to avoid
Alzheimer's disease
140
aquaporin 4
is a water channel protein primarily expressed in astrocytes that surround blood vessels in the brain. It plays a crucial role in regulating water movement between the brain interstitium, cerebrospinal fluid, and the vasculature. AQP4 facilitates the clearance of interstitial fluid and metabolites/solutes, including neurotoxic waste such as amyloid-beta, through the glymphatic system.
141
The brain is an electrochemical organ that mediates fast signaling via
mechanical- voltage- and transmitter-gated membrane ion channels
142
How does the brain transmit fast signals?
Through mechanical - voltage- and transmitter-gated membrane ion channels.
143
What are the two primary ways neurons communicate?
Electrical signaling via ion movement and chemical signaling via neurotransmitters.
144
What role do membrane ion channels play in brain function?
They regulate ion flow, affecting neuronal excitability and signal transmission.
145
What is the relationship between the brain and mechanical forces?
Mechanical forces such as intracranial pressure changes and brain pulsations can influence neural activity.
146
How does mild traumatic brain injury affect brain function?
It can cause temporary loss of consciousness, memory disruption, and confusion.
147
How do cardiac and respiratory rhythms influence the brain?
They create pulsatile forces that may affect neuronal activity.
148
What is one hypothesis for how the brain senses mechanical forces?
Specific pressure-activated ion channels transduce mechanical force into neural activity.
149
What technology allows scientists to study pressure-activated channels in neurons?
Patch-clamp recording techniques.
150
What does the cell-attached patch-clamp technique measure?
Single membrane ion channel activity.
151
Why is a tight seal between the glass electrode and membrane important in patch-clamp recordings?
It allows precise measurement of tiny ion currents.
152
What type of current can a single activated ion channel generate?
A current strong enough to depolarize the entire cell and trigger an action potential.
153
What major discovery was made in 2010 regarding mechanosensitive ion channels?
The Piezo protein family was identified as forming pressure-activated ion channels.
154
What was the significance of the MIB protein discovered in 2006?
It was later identified as Piezo1.
155
Where is Piezo2 primarily expressed?
In sensory neurons, heart, and lungs.
156
How was Piezo2 expression in the brain confirmed?
Through immunohistochemistry (IHC) and antibody validation.
157
What brain regions express Piezo2?
Neocortex, hippocampus, and cerebellum.
158
What external forces are hypothesized to activate Piezo2 in the brain?
Intracranial pressure pulsations from the heartbeat and breathing.
159
What 2012 study linked heartbeat rhythms to sensory receptor activation?
Birznieks et al. showed that muscle spindle and tactile receptors phase-lock to cardiac pulsations.
160
: How does Piezo2 contribute to sensory mechanotransduction?
It transduces mechanical stimuli into neuronal signals in the skin and muscle spindles.
161
What major challenge exists in studying brain pressure pulsations?
Distinguishing their effects from neural signals sent by the heart and blood vessels.
162
What role does the vagus nerve play in brain-heart communication?
It transmits sensory information about heart contractions and blood pressure to the brain.
163
How might heartbeat-induced oscillations function in the brain?
As a central timing mechanism for electrical oscillations.
164
What surprising discovery was made about Piezo2 expression?
It is selectively expressed in mitral cells of the olfactory bulb.
165
How was the role of Piezo2 in olfaction tested in 2024?
A mouse model with artificial blood circulation confirmed pressure sensitivity.
166
What frequency did the artificial pump generate in the olfactory bulb?
4 Hz, matching the mouse’s natural heartbeat frequency.
167
How is slow-paced breathing (resonance breathing) linked to mental health?
It can reduce anxiety and depression by modulating intracranial pressure fluctuations.
168
Why is pressure-driven communication in the brain considered energy efficient?
It uses existing heartbeat and breathing rhythms rather than active energy consumption.
169
evidence against a passive bilayer
many different lipids
membrane thickness and conformation
lipid rafts
second messenger systems
170
how was piezo discovered
by doing a cDNA library and constructing siRNA and screened until something happened
171
what would be the advantages of brain oscillation being transduced by heartbeat
fast as speed of sound 1500m/s
independent of synatptic and axonal conduction that could be contromised by drugs and degeneration
energy from heartbest instead of metabolites
